Approaches to a Key Lactone Intermediate Required for the Synthesis of Pyranonaphthoquinone Antibiotics

Abstract

Addition of 2-trimethylsilyloxyfuran (19) to naphthoquinone (20) gave in 91% yield the furo [3,2-b] naphtho [2,1-d]furan (18) which upon treatment with ceric ammonium nitrate gave the hydroxy ester (24) in 70% yield. Attempts to induce an intramolecular transesterification of hydroxy ester (24) to bislactone (6), a key intermediate required for the synthesis of several pyranonaphthoquinone antibiotics, were unsuccessful. Hydroxy ester (24), however, is closely related to the antibiotic juglomycin (32).

Synthesis of Naturally Occurring Rubilactone, Mollugin, and Dihydromollugin of Rubia cordifolia

“…Sol vent was re moved from a rotavapor, and the res i due was chromatographed on sil ica gel eluting with hexane/ethyl ac e tate (3:1) to yield methyl 1,4-dihydroxy-2naphthoate (2.7 g, 84%) as a yel low solid: mp 198-199 C (lit. 10…”

A Four-Step Total Synthesis of Radermachol

“…Our synthesis of furomollugin is outlined in Scheme . The required quinone 7 was prepared by Fischer esterification of 1,4-dihy­droxy­naphthoic acid, followed by oxidative demethylation. The reaction of 7 with butyl vinyl ether ( 2 ) gave acetal 8 in good yield.…”

“…Our first approach to radermachol is outlined in Scheme 3. Friedel−Crafts acylation of 1,4-dimethoxynaphthalene (10) with phthalic acid monomethyl ester (11) proceeded smoothly in refluxing TFAA/TFA, 16b,18 without the need for Lewis acid catalysis. CAN-mediated oxidative demethylation 19 of 12 was effective at low temperatures, giving quinone 13 in an acceptable yield; at higher temperatures the overoxidation product 14, presumably arising from conjugate addition of water to 13 and reoxidation, predominated.…”